The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
mTORC1-mediated translational elongation limits intestinal tumour initiation and growth
Open accessAbstract
Inactivation of APC is a strongly predisposing event in the development of colorectal cancer, prompting the search for vulnerabilities specific to cells that have lost APC function. Signalling through the mTOR pathway is known to be required for epithelial cell proliferation and tumour growth, and the current paradigm suggests that a critical function of mTOR activity is to upregulate translational initiation through phosphorylation of 4EBP1 (refs 6, 7). This model predicts that the mTOR inhibitor rapamycin, which does not efficiently inhibit 4EBP1 (ref. 8), would be ineffective in limiting cancer progression in APC-deficient lesions. Here we show in mice that mTOR complex 1 (mTORC1) activity is absolutely required for the proliferation of Apc-deficient (but not wild-type) enterocytes, revealing an unexpected opportunity for therapeutic intervention. Although APC-deficient cells show the expected increases in protein synthesis, our study reveals that it is translation elongation, and not initiation, which is the rate-limiting component. Mechanistically, mTORC1-mediated inhibition of eEF2 kinase is required for the proliferation of APC-deficient cells. Importantly, treatment of established APC-deficient adenomas with rapamycin (which can target eEF2 through the mTORC1–S6K–eEF2K axis) causes tumour cells to undergo growth arrest and differentiation. Taken together, our data suggest that inhibition of translation elongation using existing, clinically approved drugs, such as the rapalogs, would provide clear therapeutic benefit for patients at high risk of developing colorectal cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y.-J., Jiang, Q., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,304
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
Lessons from hereditary colorectal cancer
Kinzler, K. W., & Vogelstein, B. (1996) · Cell · doi:10.1016/s0092-8674(00)81333-1 · Cited by 4,919
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., & Clevers, H. (1997) · Science · doi:10.1126/science.275.5307.1784 · Cited by 2,905
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
A Dominant Mutation That Predisposes to Multiple Intestinal Neoplasia in the Mouse
Moser, A. R., Pitot, H. C., & Dove, W. F. (1990) · Science · doi:10.1126/science.2296722 · Cited by 1,591
The translational landscape of mTOR signalling steers cancer initiation and metastasis
Hsieh, A. C., Liu, Y., Edlind, M. P., Ingolia, N. T., Janes, M. R., Sher, A., Shi, E. Y., Stumpf, C. R., Christensen, C., Bonham, M. J., et al. (2012) · Nature · doi:10.1038/nature10912 · Cited by 1,313
Tissue‐specific and inducible Cre‐mediated recombination in the gut epithelium
El Marjou, F., Janssen, K., Hung‐Junn Chang, B., Li, M., Hindie, V., Chan, L., Louvard, D., Chambon, P., Metzger, D., & Robine, S. (2004) · genesis · doi:10.1002/gene.20042 · Cited by 1,060
Cited by
Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer
Gregorieff, A., Liu, Y., Inanlou, M. R., Khomchuk, Y., & Wrana, J. L. (2015) · Nature · doi:10.1038/nature15382 · Cited by 648
Crespo, M., Vilar, E., Tsai, S.-Y., Chang, K., Amin, S., Srinivasan, T., Zhang, T., Pipalia, N. H., Chen, H. J., Witherspoon, M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4355 · Cited by 399
Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L.-L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 399
New frontiers in translational control of the cancer genome
Truitt, M. L., & Ruggero, D. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.27 · Cited by 378
Yuan, J.-H., Liu, X.-N., Wang, T.-T., Pan, W., Tao, Q.-F., Zhou, W.-P., Wang, F., & Sun, S.-H. (2017) · Nature Cell Biology · doi:10.1038/ncb3538 · Cited by 367
Metadata
- Authors
- Faller, W. J., Jackson, T. J., Knight, J. R. P., Ridgway, R. A., Jamieson, T., Karim, S. A., Jones, C., Radulescu, S., Huels, D. J., Myant, K. B., Dudek, K. M., Casey, H. A., Scopelliti, A., Cordero, J. B., Vidal, M., Pende, M., Ryazanov, A. G., Sonenberg, N., Meyuhas, O., Hall, M. N., Bushell, M., Willis, A. E., & Sansom, O. J.
- Venue
- Nature
- Published
- 2014-11-05
- Volume
- 517
- Issue
- 7535
- Pages
- 497-500
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2046634347
- Cited by
- 302
- References
- 44
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. https://app.cochat.ai/papers/10.1038/nature13896
- The paper
- Faller, W. J., Jackson, T. J., Knight, J. R. P., Ridgway, R. A., Jamieson, T., Karim, S. A., Jones, C., Radulescu, S., Huels, D. J., Myant, K. B., Dudek, K. M., Casey, H. A., Scopelliti, A., Cordero, J. B., Vidal, M., Pende, M., Ryazanov, A. G., Sonenberg, N., Meyuhas, O., . . . Sansom, O. J. (2015). mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature. https://doi.org/10.1038/nature13896
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
